Key result
Streptokinase impairs platelet aggregation through fibrinogen depletion rather than altering glycoprotein IIb-IIIa.
Why the study?
Plasmin has been reported both to activate platelets and to inhibit platelet functions, but the mechanisms underlying these effects remain unclear.
Does plasmin generation by streptokinase or t-PA inhibit human platelet function in vitro?
Does plasmin generation by streptokinase or t-PA inhibit human platelet function in vitro?
Streptokinase, but not t-PA, at therapeutic concentrations inhibits platelet aggregation in vitro due to fibrinogen depletion and generation of fibrinogen degradation products, rather than through direct glycoprotein IIb-IIIa degradation.
BACKGROUND Plasmin has been reported both to activate platelets and to inhibit platelet functions. The latter effect was thought to be caused by proteolysis of the main membrane glycoproteins. METHODS AND RESULTS We found that incubation of citrated human platelet-rich plasma with streptokinase (SK) (300 IU/ml) does not produce any detectable activation but leads to a time-dependent inhibition of ADP-induced aggregation accompanied by substantial fibrinogenolysis. These effects were abrogated by previous addition of a plasmin inhibitor, aprotinin. Crossover experiments (SK-treated or control platelets mixed with SK-treated or control plasma) demonstrated that the platelets remained functional and that the aggregation defect was caused by fibrinogenolysis. Further experiments (addition of purified fibrinogen to fibrinogen-depleted plasma with either SK or thrombin) suggested that in addition to the low residual level of fibrinogen, fibrinogen degradation products had an inhibitory effect. Under the same conditions, tissue-type plasminogen activator (t-PA) (3,000 ng/ml) had no effect on platelet aggregation, and plasma fibrinogen was not significantly lowered. The effects on glycoproteins IIb-IIIa of incubation with SK, t-PA, or plasmin were assessed with immunoblots with murine monoclonal antibodies directed against either part of the complex, which is the receptor for fibrinogen. Proteolysis was detected only in the presence of EDTA, a potent chelator of divalent cations. CONCLUSIONS The incubation of human platelets in citrated plasma with SK concentrations obtained during therapy leads to an aggregation defect that is related to the decrease in fibrinogen, the adhesive protein involved in this function, and to the impeding effect of fibrinogen degradation products on its binding onto platelets but not to an alteration of the corresponding platelet receptor, the heterodimer glycoproteins IIb-IIIa.
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Gouin et al. (1992) studied this question. Streptokinase vs. Control was evaluated on ADP-induced aggregation and fibrinogenolysis. In vitro incubation of human platelets with streptokinase (300 IU/ml) caused an aggregation defect due to fibrinogen depletion and degradation products, without altering glycoprotein IIb-IIIa.
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